Daily Archives: January 6, 2015

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History explains why people with the malady, and their physicians, are cautious to believe that a cure is in sight

HEATHER VAN UXEM LEWIS

In 2011, a remarkable study in the New England Journal of Medicine detailed the successful treatment of six adults with haemophilia B, which is caused by a deficiency in the coagulation protein known as factor IX. All of the participants were able to eliminate or reduce the frequency of clotting-factor-replacement injectionsthe current standard treatment for the diseaseafter their livers began producing functional levels of factor IX. The experimental therapy came in the form of an adeno-associated virus (AAV) carrying a gene that encodes instructions for production of normal levels of human factor IX. Three trials of AAV-mediated gene transfer in patients with haemophilia B are ongoing, with high expectations.

After more than 20 years of research on gene transfer, it is a promising time for haemophilia therapies. It now seems likely that a single-dose treatment for haemophilia B using an AAV or another gene-transfer technique will be a viable option for many people in the next decade or two.

Yet haemophilia researchers are not inclined to speak enthusiastically of a cure. Part of that caution comes from recognition that there are still problems to solve. For example, some 40% of people with haemophilia B would find no refuge in an AAV treatment because they produce antibodies that attack and neutralize this virus.

And even if that problem were solved, the treatment would apply only to those with haemophilia B. The more common form of the condition, haemophilia A, stems from a deficit in another proteinfactor VIIIand the gene for that protein is a more difficult target. Regardless of the type of haemophilia, researchers remain hesitant about gene therapy owing to the unresolved ethical issues that arose decades ago.

The unfettered optimism that characterized the early years of gene-therapy research came to a screeching halt in 1999, when 18-year-old Jesse Gelsinger died in a phase I clinical trial at the University of Pennsylvania in Philadelphia. Gelsinger had undergone an experimental gene transfer for his otherwise treatable metabolic disorder. His death, along with a series of other harmful events in early gene-therapy trials for a variety of diseases, threatened the whole field.

Haemophilia specialists who were engaged in gene-transfer studies were more guarded than most of that era's self-proclaimed gene doctors. The source of their reserve goes beyond the cautious optimism that characterized such research after 1999; it is grounded instead in the long and troubled experience that the haemophilia community has had with technological fixes.

By the late 1970s, a therapeutic revolution had transformed haemophilia from an obscure hereditary malady into a manageable disease. But the glory of this achievement was tragically short-lived. The same clotting-factor-replacement therapies that delivered a degree of normality to the lives of people with haemophilia brought unexpected and fatal results: tens of thousands of people with haemophilia were diagnosed with transfusion-related HIV/AIDS in the 1980s and with hepatitis C virus (HCV) in the 1990s.

Excerpt from:
Gene Therapys Haemophilia Promise Is Tempered by Memories of Past Tragedies

See Inside

History explains why people with the malady, and their physicians, are cautious to believe that a cure is in sight

HEATHER VAN UXEM LEWIS

In 2011, a remarkable study in the New England Journal of Medicine detailed the successful treatment of six adults with haemophilia B, which is caused by a deficiency in the coagulation protein known as factor IX. All of the participants were able to eliminate or reduce the frequency of clotting-factor-replacement injectionsthe current standard treatment for the diseaseafter their livers began producing functional levels of factor IX. The experimental therapy came in the form of an adeno-associated virus (AAV) carrying a gene that encodes instructions for production of normal levels of human factor IX. Three trials of AAV-mediated gene transfer in patients with haemophilia B are ongoing, with high expectations.

After more than 20 years of research on gene transfer, it is a promising time for haemophilia therapies. It now seems likely that a single-dose treatment for haemophilia B using an AAV or another gene-transfer technique will be a viable option for many people in the next decade or two.

Yet haemophilia researchers are not inclined to speak enthusiastically of a cure. Part of that caution comes from recognition that there are still problems to solve. For example, some 40% of people with haemophilia B would find no refuge in an AAV treatment because they produce antibodies that attack and neutralize this virus.

And even if that problem were solved, the treatment would apply only to those with haemophilia B. The more common form of the condition, haemophilia A, stems from a deficit in another proteinfactor VIIIand the gene for that protein is a more difficult target. Regardless of the type of haemophilia, researchers remain hesitant about gene therapy owing to the unresolved ethical issues that arose decades ago.

The unfettered optimism that characterized the early years of gene-therapy research came to a screeching halt in 1999, when 18-year-old Jesse Gelsinger died in a phase I clinical trial at the University of Pennsylvania in Philadelphia. Gelsinger had undergone an experimental gene transfer for his otherwise treatable metabolic disorder. His death, along with a series of other harmful events in early gene-therapy trials for a variety of diseases, threatened the whole field.

Haemophilia specialists who were engaged in gene-transfer studies were more guarded than most of that era's self-proclaimed gene doctors. The source of their reserve goes beyond the cautious optimism that characterized such research after 1999; it is grounded instead in the long and troubled experience that the haemophilia community has had with technological fixes.

By the late 1970s, a therapeutic revolution had transformed haemophilia from an obscure hereditary malady into a manageable disease. But the glory of this achievement was tragically short-lived. The same clotting-factor-replacement therapies that delivered a degree of normality to the lives of people with haemophilia brought unexpected and fatal results: tens of thousands of people with haemophilia were diagnosed with transfusion-related HIV/AIDS in the 1980s and with hepatitis C virus (HCV) in the 1990s.

Continued here:
Gene Therapys Hemophilia Promise Is Tempered by Memories of Past Tragedies

(PRWEB) January 06, 2015

Sequencing the genomes, or entire DNA codes, of individuals to better diagnose and treat disease is a burgeoning area of research. From identifying specific genetic mistakes highly associated with certain cancers to applying effective treatments to mitigate a wayward genes effects, personalized genomic medicine is increasingly finding its way into patient care.

Harnessing the power of whole genome analysis and further defining the role of pathologists in this new era of medicine is the topic of the 2015 Benjamin Highman Lecture, sponsored by the Department of Pathology and Laboratory Medicine at UC Davis Health System.

The lecture, entitled Moving to Genomic Medicine, will be held from 5 p.m. to 6 p.m. on Thursday, Jan. 22 at the Education Building, 4610 X Street in auditorium #2222 in Sacramento. A reception will follow the presentation. Participants can register at Eventbrite.

The lecture will be presented by Debra G. B. Leonard, a leading expert in molecular pathology and genomic medicine and in applying genomic information for diagnosis and treatment of human diseases, including inherited disorders, cancers and infectious diseases.

During her presentation, Leonard will highlight the current applications for genomics and describe the various online genomic medicine resources for testing and for making patient-care decisions. She has spoken widely on various molecular pathology testing services, the future of molecular pathology and the impact of gene patents on molecular pathology practice. Leonard is professor and chair of pathology and laboratory medicine at the University of Vermont Medical Center and Physician Leader of Pathology and Laboratory Medicine at Fletcher Allen Health Care.

Making use of the massive amount of data that results from whole genome testing is an ongoing challenge for practicing physicians across disciplines, said Lydia Howell, professor and chair of pathology and laboratory medicine at UC Davis Health System. While we have the technology to quickly identify an individuals entire genetic code, which includes some three million genetic sequences, its less easy to know which genetic mistakes actually cause disease. Pathologists, with their expertise in molecular diagnostic testing, are in a unique position to lead the current movement of genomic medicine from the research bench to applications in the clinic.

The Highman Symposium is an annual lectureship in honor of Benjamin Highman, who spent almost 40 years in the U.S. Public Health Service as medical director and as chief of Pathologic Anatomy at the National Institutes of Health. He was awarded the Willey Medallion and a special citation by the U.S. Food and Drug Administration. In 1985, Highman retired and joined the volunteer faculty at the UC Davis School of Medicine.

The Department of Pathology and Laboratory Medicine includes 40 faculty and 400 academic and clinical staff who develop and deliver comprehensive diagnostic services in the fields of pathology and laboratory medicine through established and novel diagnostic modalities. Its Clinical Laboratory is home to one of the most technologically advanced testing facilities in California, providing many unique diagnostic tests unavailable elsewhere. The department processes 5 million clinical tests and 20,000 surgical pathology and 20,000 cytology specimens each year.

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UC Davis presents 2015 Benjamin Highman Lecture on genomic medicine